In recent years, cancers and cardio-circulatory diseases, e.g, hypertension, arteriosclerosis, hyperlipidemia and hypercholesteremia are increasingly becoming the major causes of death. Therefore, greater efforts and investments are being spent for the development of various medicines to treat these diseases. For example, Merck & Co., Inc. of the U.S. has developed a medicine for lowering blood cholesterol content comprising inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, which is thought to be necessary for the biosynthesis of cholesterol.
Further, Robin Schnitzer-Polokoff et al. have disclosed that an acyl CoA:cholesterol acyltransferase promotes the esterification of cholesterol in blood, suggesting that the cholesterol content in animal blood can be reduced by inhibiting the ACAT activity (Comp. Biochem. Physiol, 99A, 665-670 (1991)).
Thereafter, several ACAT inhibitors isolated from the cultures of various microorganisms have been reported as shown in Table 1 below.
TABLE 1 ______________________________________ ACAT Inhibitors ACAT inhibitor Microorganism Reference ______________________________________ Pyripyropenes Aspercillus fumigatus S. Omura et al., J. Antibiotics, 46, 1168-1169 (1993) AS-183 Scedosporium sp. K. Kuroda et al., J. Antibiotics, 46, 1196-1202 (1993) Glisoprenins Gliocladium sp. H. Tomoda et al., J. Antibiotics, 45, 1202-1206 (1992) Enniatins Fusarium sp. H. Tomoda et al., J. Antibiotics, 45, 1207-1214 (1992) Acaterin Pseudomonas sp. S. Naganuma et al., J. Antibiotics, 45, 1216-1221 (1992) Purpactins Penicillium purpurogenum H. Tomoda et al., J. Antibiotics, 44, 136-143 (1991) ______________________________________
The present inventors have endeavored to discover a novel and potent ACAT inhibitor from a culture of microorganism and, as a result, have succeeded in isolating a novel ACAT inhibitor, GERI-BP001, and its derivatives from the culture of Aspergillus fumigatus FM-F-37 which have excellent inhibitory activity against ACAT.